Nano-topographical surface engineering for enhancing bioactivity of PEEK implants (in vitro-histomorphometric study).

OBJECTIVES: Dental implants are currently becoming a routine treatment decision in dentistry. Synthetic polyetheretherketone (PEEK) polymer is a prevalent component of dental implantology field. The current study aimed to assess the influence of Nd:YAG laser nano-topographical surface engineering combined with ultraviolet light or platelet rich fibrin on the bioactivity and osseointegration of PEEK implants in laboratory and animal testing model. MATERIALS AND METHODS: Computer Aided Design-Computer Aided Manufacturing (CAD CAM) discs of PEEK were used to fabricate PEEK discs (8 mm × 3 mm) N = 36 and implant cylinders (3 mm × 6 mm) N = 72. Specimens were exposed to Nd:YAG laser at wavelength 1064 nm, and surface roughness topography/Ra parameter was recorded in nanometer using atomic force microscopy. Laser modified specimens were divided into three groups: Nd:YAG laser engineered surfaces (control), Nd:YAG laser/UV engineered surfaces and Nd:YAG laser/PRF engineered surfaces (N = 12 discs-N = 24 implants). In vitro bioactivity test was performed, and precipitated apatite minerals were assessed with X-ray diffraction analysis (XRD) and scanning electron microscopy (SEM). In vivo histomorphometric analysis was performed in rabbits with BIC% calculation. RESULTS: Ra mean value of PEEK laser engineered surfaces was 125.179 nm. For the studied groups, XRD patterns revealed distinctive peaks of different apatite minerals that were demonstrated by SEM as dispersed surface aggregations. There was a significant increase in the BIC% from control group 56.43 (0.97) to laser/UV surfaces 77.30 (0.78) to laser/PRF 84.80 (1.29) (< 0.0001). CONCLUSIONS: Successful engineered nano-topographical biomimetic PEEK implant could be achieved by Nd:YAG laser technique associated with improving bioactivity. The combination with UV or PRF could be simple and economic methods to gain more significant improvement of PEEK implant surface bioactivity with superior osteointegration.

Hyperbaric oxygen therapy efficacy on mandibular defect regeneration in rats with diabetes mellitus: an animal study.

BACKGROUND: This study aimed to investigate the influence of hyperbaric oxygen therapy on mandibular critical-sized defect regeneration in rats with experimentally induced type I diabetes mellitus. Restoration of large osseous defects in an impaired osteogenic condition such as diabetes mellitus is a challenging task in clinical practice. Therefore, investigating adjunctive therapies to accelerate the regeneration of such defects is crucial. MATERIALS AND METHODS: Sixteen albino rats were divided into two groups (n = 8/group). To induce diabetes mellitus, a single streptozotocin dosage was injected. Critical-sized defects were created in the right posterior mandibles and filled with beta-tricalcium phosphate graft. The study group was subjected to 90-min sessions of hyperbaric oxygen at 2.4 ATA, for 5 consecutive days per week. Euthanasia was carried out after 3 weeks of therapy. Bone regeneration was examined histologically and histomorphometrically. Angiogenesis was assessed by immunohistochemistry against vascular endothelial progenitor cell marker (CD34) and the microvessel density was calculated. RESULTS: Exposure of diabetic animals to hyperbaric oxygen resulted in superior bone regeneration and increased endothelial cell proliferation, which were revealed histologically and immunohistochemically, respectively. These results were confirmed by histomorphometric analysis which disclosed a higher percentage of new bone surface area and microvessel density in the study group. CONCLUSIONS: Hyperbaric oxygen has a beneficial effect on bone regenerative capacity, qualitatively and quantitively, as well as the ability to stimulate angiogenesis.

Tailored 70S30C Bioactive glass induces severe inflammation as pulpotomy agent in primary teeth: an interim analysis of a randomised controlled trial.

OBJECTIVES: This study compared clinical, histologic, and inflammatory outcomes of Biodentine and Bioactive glass (70S30C-BAG) as pulpotomy agents in primary teeth. METHODS: A randomised, clinical trial was performed recruiting 70 children, 5-9 years old, having ≥ 1 tooth indicated for vital pulpotomy. Participants were randomised to Biodentine or 70S30C-BAG groups. Clinical evaluation was scheduled at 1, 3, 6, 9, and 12 months. Additional 16 teeth were extracted after 6 weeks to assess histologic and inflammatory response (IL-8/IL-10 ratio) using ELISA. Fisher exact, Mann Whitney U test, and t test were used to compare clinical, histologic outcomes and IL-8/IL-10 ratio. RESULTS: After 3 months, 10 teeth treated with Biodentine were clinically successful, while 9 teeth treated with 70S30C-BAG failed (P < 0.001) necessitating trial termination. Causes of failure were analysed by assessing the pH and ionic release of 70S30C-BAG. Biodentine-treated teeth showed minor inflammation, normal pulp, and hard tissue formation.70S30C-BAG-treated teeth showed severe inflammation, abscesses, root resorption without hard tissue formation. There was a significantly greater percent reduction of IL-8/IL-10 ratio in Biodentine than 70S30C-BAG (mean ± SD = 66.39 ± 18.56 and 40.66 ± 0.86, P = 0.02). CONCLUSIONS: Biodentine showed favourable clinical, histologic, and anti-inflammatory outcomes, promoting pulp healing and regeneration. 70S30C-BAG resulted in pulp necrosis-through persistent inflammation-causing clinical failure. CLINICAL RELEVANCE: Biodentine is a promising pulpotomy agent in primary teeth; it promoted healing and regeneration of the dentine-pulp complex. In its current form, 70S30C-BAG is not a suitable pulpotomy agent; it induced persistent inflammation, negating the pulp ability to heal and regenerate. TRN: NCT03786302, 12/19/2018.

Formulation and evaluation of cyclodextrin-based nanosponges of griseofulvin as pediatric oral liquid dosage form for enhancing bioavailability and masking bitter taste.

The aim of this study was the development of griseofulvin (GRI) loaded ß-cyclodextrin (ß-CD) based nanosponges for bitter taste masking, improving dissolution rate and oral bioavailability. Plain NS (NS1 NS2 and NS3) were fabricated by reacting ß-CD with the cross-linker diphenyl carbonate at different molar ratios (1:2, 1:4 and 1:6, respectively) using ultrasonication method. The NS2 provided both highest %yield and GRI solubilization enhancement. Thus, the drug was loaded in NS2 at different NS2: drug weight ratios in presence or absence of 0.25%w/w polyvinylpyrolidone (PVP k30). The GRI loaded NS (F1) that provided highest drug loading capacity and entrapment efficiency (47.20 ± 0.38%, 84.91 ± 0.30%, respectively) was morphologically examined using scanning electron microscopy (SEM). Also, Particle size, zeta potential, differential scanning calorimetry (DSC), Fourier transform infra-red (FT-IR), nuclear magnetic resonance (NMR) spectroscopy, in-vitro release, taste masking potential were evaluated. Moreover, in-vivo Pharmacokinetic studies were performed on rats. The F1 showed particle size 665.9 ± 13.8 nm and zeta potential -21.5 ± 0.7 mV. The DSC and FT-IR analysis confirmed the complexation of GRI with NS2. Nanosponges (F1) provided 3.19, folds increase in dissolution efficiency %, 2.13 and 3.78 folds increase in Cmax and AUC0-48 compared to plain GRI. Taste masking evaluation confirmed the potential of GRI nanosponges (F1) in masking the bitter taste of GRI completely. The study confirmed that complexation of GRI with NS would be a viable approach for masking the bitter taste of GRI and improving oral bioavailability, that Cmax, Tmax and AUC 0-48 were significantly higher for the developed formulation (F1).

Eco-friendly synthesis of functionalized chitosan-based nanoantibiotic system for potential delivery of linezolid as antimicrobial agents.

To obtain a healthy human being with beneficial microflora against different pathogenic infections, classical antibiotics with nanosized biomaterials were used to inhibit the growth of bacterium by their potent synergistic effect. Hence, this study planned to load an oxazolidinone antibiotic named linezolid (LD) onto functionalized chitosan (CN) with 3, 5- dinitrosalyslic acid (DA) via microwave synthesis without harsh condition. The exploring synergistic effect of linezolid (LD) with CN/DA controllable nanostructure was compact efflux-mediated methicillin-resistant Staphylococcus aureus (MRSA) burden and other selected bactericide Gram-positive ((S. aureus), Gram-negative (E. coli), Fungi (C. albicans), Yeast (A. niger), and E. faecalis. The obtained results showed that LD was incorporated into both the internal and external surface of the aggregated CN/DA nanosystem with an average diameter of 150 nm ± 4 hints of the drug loading. Owing to the nature of functionalized CN, the release efficiency attains 98.4% within 100 min. The designed LD@CN/DA exhibited inhibition zone 54 mm, 59 mm, 69 mm, 54 mm, 57 mm, and 24 mm against the tested microbes respectively rather than individual LD. The major target of the current research is achieved by using LD@CN/DA as a nanoantibiotic system that has exceptional consistently active against multi-resistant pathogens, in between MRSA which resist LD. Also, cell viability was performed even after three days of direct cell culture on the surface of the designed nanoantibiotic. The mechanism of microbial inhibition was correlated and rationalized to different charges and the presence of oxygen species against microbial infections. Our findings provide a deep explanation about nanostructured antibiotics design with enhanced potentially pathogen-specific activity.

Comparison of remineralization by fluoride varnishes with and without casein phosphopeptide amorphous calcium phosphate in primary teeth.

OBJECTIVE: To compare MI (5% NaF with 2% CPP-ACP) and Prevident (5% NaF) varnishes in remineralizing caries-like lesions in primary teeth regarding calcium and phosphate enamel content and lesion depth. MATERIAL AND METHODS: Caries-like lesions were created in 48 primary teeth which were divided into 2 halves; one left untreated (control) and the other half treated with MI or Prevident varnishes. Calcium and phosphate content was assessed using energy dispersive X-ray spectrometer and reduction in lesion depth was assessed using polarized light microscopy. Demineralization and remineralization values in each group were compared using paired t test and percentage change between groups was compared using t test and Mann Whitney U test. RESULTS: A greater percentage increase of calcium was observed in MI than Prevident specimens (median = 8.97 and 2.67, p < .0001), with greater calcium phosphate ratio percentage increase (median = 28.96 and 7.40) and phosphate percentage reduction (median = 15.5 and 4.51). The mean (SD) percentages reduction in lesion depth in the MI varnish was significantly greater than in Prevident varnish (44.41 (7.12) and 22.73 (9.35), p < .0001). CONCLUSIONS: MI varnish had better remineralization effect in primary teeth than Prevident varnish in terms of higher mineral content and shallower lesion depth.

Transdermal patches loaded with L-cysteine HCL as a strategy for protection from mobile phone emitting electromagnetic radiation hazards.

Mobile phone usage has been increased in the last few years emitting electromagnetic radiation (EMR), which disturbs normal cellular processes via oxidative stress. L-cysteine, a glutathione precursor, prevents oxidative damage. Transdermal patches (TDPs) loaded with L-cysteine hydrochloride (L-CyS-HCL) were fabricated by dispersion of L-CyS-HCL 5% w/w and different concentrations of sorbitol as a plasticizer in room-temperature vulcanizable synthetic silicone matrices (RTV-Si). The effect of sorbitol on patch physicochemical parameters was assessed; in-vitro L-CyS-HCL release profiles and ex-vivo permeation were studied. Pharmacokinetic parameters of endogenous synthetized in-vivo glutathione, after receiving IV bolus dose of L-CyS-HCl and L-CyS-HCl-RTV-Si-TDPs were studied in rat model. The influence of L-CyS-HCL-RTV-Si-TDPs against damaging effects of mobile phone EMR on rats' blood and brain tissues was studied. The results revealed that patch plasticity, intensity reflections, surface porosity, L-CyS-HCL release rate and skin permeation increased with increasing sorbitol concentration. Pharmacokinetic profile for IV dose and L-CyS-HCl-RTV-Si-TDPs revealed that the L-CyS-HCl-RTV-Si-TDPs provided a sustained glutathione plasma concentration-time profile over entire patch application. High significant differences in biological parameters (blood and brain samples) were observed for radiated rats using the patch in study compared with positive control rats. Promising long-term strategy for protection against mobile phone hazards was obtained.

Correction to: Preparation and Optimization of Fast-Disintegrating Tablet Containing Naratriptan Hydrochloride Using D-Optimal Mixture Design.

During the production process, an editorial error occurred where the typesetter placed the ± symbol on the right side of the values in Table IV, whereas the symbol should be placed on the left side. The original article has been corrected.

Preparation and Optimization of Fast-Disintegrating Tablet Containing Naratriptan Hydrochloride Using D-Optimal Mixture Design.

Optimization of a lyophilized fast-disintegrating tablet (LFDT) formulation containing naratriptan hydrochloride, an antimigraine drug, was the foremost objective of the study, aiming in achieving fast headache pain relief. The Design-Expert® v10 software was used to generate formulations using D-optimal mixture design with four components: gelatin (X1), hydrolyzed gelatin (X2), glycine (X3), and mannitol (X4) of total solid material (TSM) w/w. The effect of the relative proportion of each component was determined on friability (Y1), hardness (Y2), and in vitro disintegration time (Y3), which was then applied for formulation optimization. In addition, their effect on tablet porosity was determined via scanning electron microscopy (SEM). Drug-excipient interaction was evaluated using differential scanning calorimetry (DSC). A comparative dissolution study against the conventional tablets was studied. Accelerated stability study was carried out in (Al/Al) and (Al/PVC) blister packs. An in vivo pharmacokinetic study was carried out to compare the optimized formulation and the conventional tablets. The optimized formulation's responses were 0.30%, 3.4 kg, and 6.12 s for Y1, Y2, and Y3, respectively. No drug-excipient interaction was specified via DSC. The optimized formulation exhibited porous structure as determined via SEM. Dissolution study demonstrated complete dissolution within 1.5 min. Study indicated stability for 78 months in (Al/Al) blister packs. In vivo pharmacokinetic study demonstrated that Cmax, AUClast, and AUCinf were significantly higher for the developed formulation. As well, the Tmax was 1 h earlier than that of convenient tablet. An LFDT would achieve a faster onset of action for naratriptan compared to other formulations.

Design of Isoniazid Smart Nanogel by Gamma Radiation-Induced Template Polymerization for Biomedical Application.

PURPOSE: Preparation of Isoniazid (INH) loaded nanogel particles using gamma radiation as safe, simple, cheap and reproducible technique for promoting mycobacterial killing in a lower-dose system aiming in developing of drug resistance. METHODS: Polymeric pH-sensitive nanogels were prepared by gamma radiation-induced polymerization of Acrylic acid (AAc) or Itaconic acid (IA), in aqueous solution of polyvinylpyrrolidone (PVP), as template polymer. The prepared nanogels were utilized for encapsulation of INH. 31X22 factorial design was employed for optimization and exploring the effect of radiation dose (X1) (30-50kGy), ratio of PVP: acid (X2) (50:50-30:70) and type of acid (X3) on the prepared nanogel characterization RESULTS: The optimized levels of X1, X2 and X3 were (50 KGy, 30:70 and Itaconic acid, respectively), with a desirability of 0.959. In-vitro INH release rate from the prepared nanogels decreased with increasing gamma radiation doses, with the predominance of the diffusion mechanism for drug release pattern. In addition, it was perceived that the minimum inhibitory concentration (MIC) of INH loaded PVP/PIA nanogels on Mycobacteria Tuberculosis was 8 folds lower than that of INH solution. CONCLUSION: The prospective of PVP-K90/PIA was recommended as a smart candidate for delivery of INH with promising achievements against tuberculosis than free drug. Graphical abstract Mechanism of formation and loading of Isoniazid PVP/PIA nanogel.

Modulating liposomal nanoparticles to enhance uptake and targeting of methicillin-resistant Staphylococcus aureus.

Aims: To explore the role of modifying the phospholipid composition of liposomal nanoparticles (LNPs) on their uptake. Methods: Different LNPs were labeled with a fluorescent marker and their uptake by human lung fibroblast (WI-38) cells was evaluated using flow cytometry and confocal microscopy. Linezolid was loaded in LNPs showing enhanced uptake, and their ability to reduce intracellular methicillin-resistant Staphylococcus aureus (MRSA) was investigated by in vitro infection. Results: Liposomes with disaturated dipalmitoylphosphatidylcholine-phosphatidylglycerol-phosphatidylethanolamine at a molar ratio of 60:10:10, mimicking that of WI-38 cells, were more effectively uptaken. Linezolid-loaded LNPs significantly reduced intracellular MRSA viable count. Conclusion: Modified LNPs could be promising antibiotic nanocarriers for targeting intracellular MRSA, which are usually resistant to conventional antibiotics.

Liposomal nanoparticles (LNPs) are considered effective drug-delivery nanocarriers. We investigated the effect of altering the phospholipid composition of LNPs on their uptake into lung cells. Intracellular uptake of LNPs with different phospholipids was evaluated. LNPs showing enhanced uptake were loaded with linezolid antibiotic and their potential to kill the intracellular bacteria was explored as the difficulty for an antibiotic to reach the intracellular bacteria results in treatment failure. LNPs with phospholipid composition similar to that of the lung cells were effectively uptaken and were also able to deliver linezolid into lung cells and kill the intracellular bacteria. This approach could be successfully applied to reduce the antibiotic dose and subsequently overcome antibiotic resistance.

Electronic cigarettes can damage lingual papillae and taste buds. Can vitamins C and E supplementation reverse this damage?

AIMS: This histological study focuses on the impact of electronic cigarette liquid (EC) on lingual papillae, especially taste buds, compare it to nicotine, and investigates the potential of vitamins in reversing these unwanted changes. MAIN METHODS: 40 adult male rats were allocated into 5 groups. Control injected saline intraperitoneally, electronic cigarettes group injected EC-liquid containing nicotine of dose (0.75 mg/kg), electronic cigarette group injected EC-liquid then supplemented orally with vitamins C and E, nicotine group injected pure nicotine of dose (0.75 mg/kg) and lastly nicotine group injected with pure nicotine of dose (0.75 mg/kg) then supplemented orally with vitamins C and E. Keratin surface area and the ratio between taste buds and its epithelial covering surface areas in fungiform papillae were measured. KEY FINDINGS: Histological examination of EC group revealed abnormal epithelial stratification and mitotic figs. EC plus V group showed intact basal cell layer. N group showed better histological stratification than EC group. Fungiform and circumvallate papillae in EC and N groups showed distorted appearance of taste buds. Histomorphometry analysis showed a significant decrease in taste buds to epithelium surface areas in EC, nicotine, and EC plus V groups, p-value (<0.05). There was no significant difference between control and N plus V groups. SIGNIFICANCE: Administration of vitamins C and E showed preservation of normal histological features of the lingual mucous membrane. EC caused striking damage to taste buds even after the administration of vitamins. The negative effects of electronic cigarettes are not confined only to the presence of nicotine.

Role of a medical student neuro-society organized neurosurgical conference: The Glasgow neuro experience.

Background: Entering neurosurgical training in the United Kingdom demands extensive prior commitment and achievement, despite little to no exposure to the specialty in medical school. Conferences run by student "neuro-societies" offer a means to bridge this gap. This paper describes one student-led neuro-society's experience of curating a 1-day national neurosurgical conference supported by our neurosurgical department. Methods: A pre-and post-conference survey was distributed to attendees to ascertain baseline opinions and conference impact using a five-point Likert Scale, and free text questions explored medical students' opinions of neurosurgery and neurosurgical training. The conference offered four lectures and three workshops; the latter provided practical skills and networking opportunities. There were also 11 posters displayed throughout the day. Results: 47 medical students participated in our study. Post-conference, participants were more likely to understand what a neurosurgical career involves and how to secure training. They also reported increased knowledge about neurosurgery research, electives, audits, and project opportunities. Respondents enjoyed the workshops provided and suggested the inclusion of more female speakers in future. Conclusion: Neurosurgical conferences organized by student neuro-societies successfully address the gap between a lack of neurosurgery exposure and a competitive training selection. These events give medical students an initial understanding of a neurosurgical career through lectures and practical workshops; attendees also gain insight into attaining relevant achievements and have an opportunity to present research. Student neuro-society-organized conferences have the potential to be adopted internationally and used as a tool to educate on a global level and greatly aid medical students who are aspiring neurosurgeons.

Evaluation of the combination effect of rutin and vitamin C supplementation on the oxidative stress and inflammation in hemodialysis patients.

Background: Hemodialysis (HD) patients are at risk of malnutrition, cardiovascular complications, and all-cause mortality due to oxidative stress and inflammation. Some studies have demonstrated that rutin attenuates oxidative stress and inflammation in CKD rats, but its effects in HD patients are unknown to date. Aim: The aim of this study was to evaluate the effect of rutin and vitamin C versus vitamin C alone on oxidative stress and inflammation in HD patients. Methods: A prospective randomized, open-label, controlled trial enrolled on hundred and five HD patients divided into three groups as follows: patients in group 1 were given a rutin/vitamin C combination (Ruta C group as the combination trade name is known as Ruta C 60 tablets), patients in group 2 were given vitamin C (1 g) (vitamin C group), and group 3 was the control group; the study period was 16 weeks. The following were assessed at baseline and at the end of the study: serum malondialdehyde (MDA), glutathione peroxidase (GPx), high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), lipid profile levels, and erythrocyte sedimentation rate. Results: It was found that vitamin C significantly increased serum GPx in group 2 (p = 0.001) compared to a non-significant result in both group 1 and 3; in addition, serum MDA and TNF-α values had decreased significantly in the three groups compared to their baselines; however, a non-significant difference was seen among the studied groups at the end of the study. On the other hand, MDA levels were reduced by 50% in interventional groups compared to 28% in the control group, while the Ruta C group showed an 80% reduction in the level of TNF α compared to the 78% reduction observed in the vitamin C group, and finally, the interventional drugs showed a significant improvement in the lipid profile. Conclusion: Vitamin C supplementation alone for 16 weeks had a potential effect on the antioxidant's GPx activity. Moreover, it was reported that both vitamin C alone or the rutin/vitamin C combination (Ruta C) showed a protective role against lipid peroxidation, evidenced by the reduced levels of MDA. Finally, rutin had a favorable synergistic effect with vitamin C in reducing TG and TNF-α levels and increasing HDL-C level.

Effect of high molecular weight hyaluronic acid in treatment of osteoarthritic temporomandibular joints of rats.

OBJECTIVE: The aim of this study was to determine the histological and biochemical effects of high molecular weight hyaluronic acid on experimentally induced osteoarthritic changes in male rat temporomandibular joint (TMJ). DESIGN: In this in-vivo study, 36 male albino rats were divided into 3 groups; control non-injected, disease and treatment group. Osteoarthritis was induced using a single intra-articular injection of Complete Freund's adjuvant (CFA) (50 µl). High molecular weight hyaluronic acid (HMWHA) was injected intra-articularly once a week, for a total of 3 injections. TMJ tissue samples were dissected from control, disease and treatment groups for biochemical analysis using ELISA test to detect the levels of matrix metalloproteinase-3 (MMP-3) on day 28. Histological examination was done using Hematoxylin &eosin, Mallory's trichrome and Alcian blue stains. Data was analyzed using Kruskal-Wallis test followed by Dunn-Sidek method, with a 5 % significance level. RESULTS: Treatment group showed regaining of the normal histological features of the TMJ and decreased levels of MMP-3 when compared to disease group. CONCLUSIONS: These findings may suggest that HMWHA plays a role in the management of CFA-induced osteoarthritic cartilage lesions.

Pulmonary Delivery of Isoniazid in Nanogel-Loaded Chitosan Hybrid Microparticles for Inhalation.

PURPOSE: Inhalable pulmonary delivery of isoniazid (INH) may improve the efficacy and reduce drug resistance. METHOD: INH-loaded chitosan microparticles (Cs-Mps-1-3) were prepared as an inhalable carrier for the previously prepared INH-loaded polyvinylpyrrolidone/polyitaconic acid nanoparticles (NPs) using spray-drying technique. Here, Cs-Mps-1-3 are composed of Cs: INH-loaded NPs: Free INH at w/w ratios (1:1:0), (1: 0:1), and (1:1:1), respectively. Subsequently, the prepared Cs-Mps-1-3 characterizations were studied. RESULTS: Cs-Mps-1-3 showed a spherical, smooth, positively charged surface (ζ-potential values +20.2, +28.7, and +22.6) and a size range 1.52-3.12 µm. In addition, Carr's compressibility indices of Cs-Mps-1-3 were 32.5%, 24.8%, and 28.02%, respectively. The in vitro INH released showed good correlation with first-order pattern, with predominance of the diffusion-controlled mechanism. In vitro aerodynamic deposition of Cs-MPs-3 possessed 56.81% effective fine particle fraction with lower impaction loss and device retention (10.47% and 30.9% at mouth and throat and at stage 1, respectively). The minimum inhibitory concentration of Cs-Mps-3 displayed 63-fold more inhibition effects on Mycobacterium tuberculosis than INH solution, owing to the combined effect of positively charged Cs-Mps with their facilitating bacterial cell surface binding and cellular penetration activity of NPs. CONCLUSION: The promising potential of Cs-Mps-3 as an inhalable carrier for pulmonary delivery of INH is recommended.

Adaptation of hard gelatin capsules for oral delivery of aqueous radiopharmaceuticals.

PURPOSE: Oral administration of Iodine-131 (I-131) solutions causes high risk of contamination for patients and dispensers. The objective of the study was to adapt hard gelatin capsules (HGCs) for filling with radiopharmaceutical solutions without deformation. METHODS: Polystyrene (PS) internally lining films with different thicknesses were used to protect HGCs. The insulated HGCs were evaluated for their physicochemical characteristics and rupturing time in different dissolution media. HGCs internally lined with PS were examined for withstand loading with different volumes and radioactivities of I-131 solutions. Radioactivity release was studied in deionized water and acidic media. Quality control of released I-131 was inspected for radiochemical purities. RESULTS: There was a directly proportion between PS lining thickness and stability of HGCs after filling with 500 µl aqueous methylene blue solution. HGCs internally lined with PS 100 µm thickness withstand deformation for ˃ two months; however showed fast in-vitro rupturing time in different dissolution media. Internally lined HGCs loaded with different volumes and radioactivities of I-131 solutions resisted for one week without radioactive leakage. Yet, revealed complete release of I-131 after 20 min in dissolution media with great radiochemical purity. CONCLUSION: The study promises safely I-131 aqueous solution delivery via adapted HGCs. Graphical abstract Oral administration of radiopharmaceuticals.

Fabrication Of Gold Nanoparticles In Absence Of Surfactant As In Vitro Carrier Of Plasmid DNA.

PURPOSE: This work aimed to synthesize surfactant-free AuNPs for targeted delivery of plasmid DNA encoded p53 gene and to avoid conventional production method of Gold nanoparticles (AuNPs) which may adversely affect the final shape, diversity, and size due to accumulation of the formulated surfactant - gold complex to the surface. METHODS: The AuNPs were fabricated using seeded-growth method with L-Cystine methyl ester hydrochloride as capping agent, then loaded with plasmid DNA encoded p53 gene. The resultant AuNPs and AuNPs-p53 complex were evaluated for physical characteristics and morphology. Confirmation of complex formation was performed using gel electrophoresis. Furthermore, the efficient delivery and cytotoxicity behavior of the encoded gene were examined on both healthy lung cells (WI38) and cancerous lung cells (A549). RESULTS: L-cysteine methyl ester hydrochloride AuNPs showed acceptable physical characteristics (30 nm, +36.9 mv, and spherical morphology). P53 attachment to AuNPs was confirmed by gel electrophoresis. The RT-PCR proved the overexpression of p53 by the fabricated AuNPs-p53 complex. The high percentage of cell viability in normal lung cell line (WI 38) proved the safety of L-cysteine methyl ester functionalized AuNPs. Additionally, the apoptotic effect due to expression of p53 gene loaded on AuNPs was only prominent in lung cancer cell line (A549), revealing selectivity and targeting efficiency of anticancer AuNPs-p53 complex. CONCLUSION: AuNPs can be considered as a potential delivery system for effective transfection of plasmid DNA which can be used for successful treatment of cancer.

Stabilized tetraether lipids based particles guided prophyrins photodynamic therapy.

Photodynamic therapy (PDT) that involves ergonomically delivered light in the presence of archetypical photosensitizer such as Protoporphyrin IX (PpIX) is a time-honored missile strategy in cancer therapeutics. Yet, the premature release of PpIX is one of the most abundant dilemma encounters the therapeutic outcomes of PDT due to associated toxicity and redistribution to serum proteins. In this study, ultrastable tetraether lipids (TELs) based liposomes were developed. PpIX molecules were identified to reside physically in the monolayer; thereby the inherent π-π stacking that leads to aggregation of PpIX in aqueous milieu was dramatically improved. TEL29.9 mol% and TEL62mol% based liposomes revealed PpIX sustained release diffusion pattern from spherical particles as confirmed by converged fitting to Baker & Lonsdale model. Stability in presence of human serum albumins, a key element for PDT accomplishment was emphasized. The epitome candidates were selected for vascular photodynamic (vPDT) in in-Ovo chick chorioallantoic membrane. Profoundly, TEL62mol% based liposomes proved to be the most effective liposomes that demonstrated localized effect within the irradiated area without eliciting quiescent vasculatures damages. Cellular photodynamic therapy (cPDT) revealed that various radiant exposure doses of 134, 202, 403 or 672 mJ.cm-2 could deliberately modulate the photo-responses of PpIX in TEL-liposomes.

Colon-specific drug delivery for mebeverine hydrochloride.

Mebeverine Hydrochloride (MB-HCl), an effective spasmolytic drug, was formulated as CODES. A colon-specific drug delivery technology CODES was designed to avoid the inherent problems associated with pH- or time-dependent systems. To achieve more protection and control of drug release, MB-HCl was prepared as microspheres and compressed as core tablets of CODES (modified CODES). The core tablets contained the drug either in free form [Formula 1 (F(1))], or as microspheres with 2 different polymer:drug:lactulose ratios (1:1:0.5 [Formula 2 (F(2))] and 2:1:0.5 [Formula 3 (F(3))]. The release profiles of the coated CODES systems were compared with uncoated compressed tablets. The uncoated tablet showed a drug release of 94% after 1 h in simulated gastric condition (pH = 1.2). The release characteristics of the coated systems revealed that the enteric coating (Eudragit L(100)) prevented any drug release in simulated gastric or duodenal conditions in the first 3 h (pH 1.2-6.1), after which drug was slightly liberated in simulated intestinal fluid (pH 7.4) {Phase 1 (P1)}. After 4 h the pH was adjusted to 7 and beta-glucose-oxidase was added, which is an enzyme produced by enterobacteria present in the colon. The acid-soluble coat (Eudragit)E(100)) dissolved and the drug release suddenly increased to reach 95, 72 and 60.4% for F(1)-F(3), respectively. IR spectrum study showed a covalent bond between the drug and the polymer in the formulae F(2) and F(3) resulting in the sustained drug release from the microspheres with a significant difference (p>0.05) to F(1). The findings were confirmed by in vivo investigation using X-ray images for Guinea pigs ingested tablets containing barium sulphate (F(4)), where the tablet began to disintegrate after 10 h of tablet intake. The results of the study indicated that MB-HCl CODES colon-specific drug delivery can act as a successful trigger for drug targeting in the colon. Furthermore, a sustained release of the drug can be achieved from modified CODES containing the drug in the form of microspheres.